There have been many success stories for immune checkpoint blockade therapies, both in preclinical models and in patients with cancer. But many questions remain about exactly how such immunotherapies elicit their response and what determines when and where checkpoint blockade therapy succeeds or fails at reinvigorating the immune system to eradicate cancer. A new study led by investigators from Brigham and Women's Hospital in Boston, in collaboration with colleagues at the Broad Institute, also in Boston, examines the effects of immune checkpoint blockade therapies on different populations of T-cells, a key class of immune cells in tumors. The team's surprising results point to a population of T-cells that has been overlooked in the past and have led to the identification of a molecular factor that may be predictive of response to treatment. The investigators' findings were published online on January 8, 2019 in Immunity. The article is titled “Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1−CD8+ Tumor-Infiltrating T Cells.” "Our study takes advantage of the observation that there is great diversity in the T-cells within tumors. When we looked at the effect of therapies on different cell populations, we were surprised and puzzled to find that even T-cells that don't express checkpoint inhibitors showed significant changes at the genetic level," said co-corresponding author Ana Anderson (photo), PhD, Associate Scientist at the Brigham, and Associate Professor of Neurology at Harvard Medical School. "These are cells that have largely been ignored before. Our study broadens the focus of what checkpoint blockade therapy may be doing and how it mediates its effects." Dr.